No small feat: microRNA responses during vocal communication in songbirds

Simply hearing the song produced by another bird of the same species triggers the regulation of microRNAs (miRNAs) in high-order auditory parts of the zebra finch brain. Some of the identified miRNAs appear to be unique to birds, possibly to songbirds. These findings, reported in BMC Genomics, highlight the complexities of gene regulation associated with vocal communication and point to possible key regulators of song-triggered gene networks

3D Scanning System for Automatic High-Resolution Plant Phenotyping

Thin leaves, fine stems, self-occlusion, non-rigid and slowly changing structures make plants difficult for three-dimensional (3D) scanning and reconstruction -- two critical steps in automated visual phenotyping. Many current solutions such as laser scanning, structured light, and multiview stereo can struggle to acquire usable 3D models because of limitations in scanning resolution and calibration accuracy. In response, we have developed a fast, low-cost, 3D scanning platform to image plants on a rotating stage with two tilting DSLR cameras centred on the plant. This uses new methods of camera calibration and background removal to achieve high-accuracy 3D reconstruction. We assessed the system's accuracy using a 3D visual hull reconstruction algorithm applied on 2 plastic models of dicotyledonous plants, 2 sorghum plants and 2 wheat plants across different sets of tilt angles. Scan times ranged from 3 minutes (to capture 72 images using 2 tilt angles), to 30 minutes (to capture 360 images using 10 tilt angles). The leaf lengths, widths, areas and perimeters of the plastic models were measured manually and compared to measurements from the scanning system: results were within 3-4% of each other. The 3D reconstructions obtained with the scanning system show excellent geometric agreement with all six plant specimens, even plants with thin leaves and fine stems.Comment: 8 papes, DICTA 201

Conserved syntenic clusters of protein coding genes are missing in birds

BACKGROUND: Birds are one of the most highly successful and diverse groups of vertebrates, having evolved a number of distinct characteristics, including feathers and wings, a sturdy lightweight skeleton and unique respiratory and urinary/excretion systems. However, the genetic basis of these traits is poorly understood. RESULTS: Using comparative genomics based on extensive searches of 60 avian genomes, we have found that birds lack approximately 274 protein coding genes that are present in the genomes of most vertebrate lineages and are for the most part organized in conserved syntenic clusters in non-avian sauropsids and in humans. These genes are located in regions associated with chromosomal rearrangements, and are largely present in crocodiles, suggesting that their loss occurred subsequent to the split of dinosaurs/birds from crocodilians. Many of these genes are associated with lethality in rodents, human genetic disorders, or biological functions targeting various tissues. Functional enrichment analysis combined with orthogroup analysis and paralog searches revealed enrichments that were shared by non-avian species, present only in birds, or shared between all species. CONCLUSIONS: Together these results provide a clearer definition of the genetic background of extant birds, extend the findings of previous studies on missing avian genes, and provide clues about molecular events that shaped avian evolution. They also have implications for fields that largely benefit from avian studies, including development, immune system, oncogenesis, and brain function and cognition. With regards to the missing genes, birds can be considered ‘natural knockouts’ that may become invaluable model organisms for several human diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0565-1) contains supplementary material, which is available to authorized users

A feasibility study for NOn-Traditional providers to support the management of Elderly People with Anxiety and Depression: the NOTEPAD study Protocol

BACKGROUND: Anxiety and depression are common among older people, with up to 20% reporting such symptoms, and the prevalence increases with co-morbid chronic physical health problems. Access to treatment for anxiety and depression in this population is poor due to a combination of factors at the level of patient, practitioner and healthcare system. There is evidence to suggest that older people with anxiety and/or depression may benefit both from one-to-one interventions and group social or educational activities, which reduce loneliness, are participatory and offer some activity. Non-traditional providers (support workers) working within third-sector (voluntary) organisations are a valuable source of expertise within the community but are under-utilised by primary care practitioners. Such a resource could increase access to care, and be less stigmatising and more acceptable for older people. METHODS: The study is in three phases and this paper describes the protocol for phase III, which will evaluate the feasibility of recruiting general practices and patients into the study, and determine whether support workers can deliver the intervention to older people with sufficient fidelity and whether this approach is acceptable to patients, general practitioners and the third-sector providers. Phase III of the NOTEPAD study is a randomised controlled trial (RCT) that is individually randomised. It recruited participants from approximately six general practices in the UK. In total, 100 participants aged 65 years and over who score 10 or more on PHQ9 or GAD7 for anxiety or depression will be recruited and randomised to the intervention or usual general practice care. A mixed methods approach will be used and follow-up will be conducted 12 weeks post-randomisation. DISCUSSION: This study will inform the design and methods of a future full-scale RCT. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN16318986 . Registered 10 November 2016. The ISRCTN registration is in line with the World Health Organization Trial Registration Data Set. The present paper represents the original version of the protocol. Any changes to the protocol will be communicated to ISRCTN

An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression

TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors. Significance: We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy

Psychological and pharmacological interventions for post-traumatic stress disorder and comorbid mental health problems following complex traumatic events: systematic review and component network meta-analysis

Background: Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at not only at risk of post-traumatic stress disorder (PTSD) but also other mental health comorbidities. While evidence-based psychological and pharmacological treatments are effective for single event PTSD it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events.Methods and Findings: We searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised and non-randomised controlled trials of psychological and pharmacological treatments for PTSD symptoms n people exposed to complex traumatic events, published up to 25th October 2019. We adopted a non-diagnostic approach and included studies of adults who have experienced complex trauma. Complex trauma sub-groups were: veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs for a total of 6158 participants were included in meta-analyses across the primary and secondary outcomes; 19 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ±9.3 years, and 42% were male. Nine non-randomised controlled trials were included. The mean age of participants in the non-randomised controlled trials was 40.6 ±9.4 years, and 47% were male. The average length of follow-up across all included studies at post-treatment for the primary outcome was 11.5 weeks. The pair-wise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k=46; n=3389; standardised mean difference, SMD=-0.82, 95% CI: -1.02 to -0.63) and active control (k-9; n=662; SMD=-0.35, 95% CI: -0.56 to -0.14) at post-treatment, and also compared with inactive control at 6-month follow-up (k=10; n=738; SMD=-0.45, 95% CI: -0.82 to -0.08). Psychological interventions reduced depressive symptoms (k=31; n=2075; SMD=-0.87, 95% CI: -1.11 to -0.63; I2=82.7%, p=0.000) and anxiety (k=15; n=1395; SMD=-1.03, 95% CI: -1.44 to -0.61; p=0.000) at post-treatment comparted with inactive control. Sleep quality was significantly improved at post-treatment by psychological interventions compared with inactive control (k=3; n=111; SMD=-1.00, 95% CI: -1.49 to-0.51; p=0.245). There were no significant differences between psychological interventions and inactive control group at post-treatment for quality of life (k=6; n=401; SMD=0.33, 95% CI: -0.01 to 0.66; p=0.021). Antipsychotic medicine (k=5; n=364; SMD=–0.45; –0.85 to –0.05; p=0.085) and Prazosin (k=3; n=110; SMD=-0.52; -1.03 to -0.02; p=0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower drop out, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma focused interventions across trauma sub-groups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multi-component interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k=17; n=1077; mean difference=-37.95, 95% CI: -60.84 to -15.16). Our use of a non-diagnostic inclusion strategy may have over-looked certain complex trauma populations with severe and enduring mental comorbidities. Additionally, the relative contribution of skills-based intervention components were not feasibly evaluated in the network meta-analysis.Conclusions: In this systematic review and meta-analysis we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multi-component interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority

phenix.model_vs_data: a high-level tool for the calculation of crystallographic model and data statistics

Application of phenix.model_vs_data to the contents of the Protein Data Bank shows that the vast majority of deposited structures can be automatically analyzed to reproduce the reported quality statistics. However, the small fraction of structures that elude automated re-analysis highlight areas where new software developments can help retain valuable information for future analysis

What work has to be done to implement collaborative care for depression? Process evaluation of a trial utilizing the Normalization Process Model

<p>Abstract</p> <p>Background</p> <p>There is a considerable evidence base for 'collaborative care' as a method to improve quality of care for depression, but an acknowledged gap between efficacy and implementation. This study utilises the Normalisation Process Model (NPM) to inform the process of implementation of collaborative care in both a future full-scale trial, and the wider health economy.</p> <p>Methods</p> <p>Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory randomised controlled trial of a collaborative model of care for depression.</p> <p>Results</p> <p>Findings are presented as they relate to the four factors of the NPM (interactional workability, relational integration, skill-set workability, and contextual integration) and a number of necessary tasks are identified. Using the model, it was possible to observe that predictions about necessary work to implement collaborative care that could be made from analysis of the pre-trial data relating to the four different factors of the NPM were indeed borne out in the post-trial data. However, additional insights were gained from the post-trial interview participants who, unlike those interviewed before the trial, had direct experience of a novel intervention. The professional freedom enjoyed by more senior mental health workers may work both for and against normalisation of collaborative care as those who wish to adopt new ways of working have the freedom to change their practice but are not obliged to do so.</p> <p>Conclusions</p> <p>The NPM provides a useful structure for both guiding and analysing the process by which an intervention is optimized for testing in a larger scale trial or for subsequent full-scale implementation.</p

A New Chicken Genome Assembly Provides Insight into Avian Genome Structure

The importance of the Gallus gallus (chicken) as a model organism and agricultural animal merits a continuation of sequence assembly improvement efforts. We present a new version of the chicken genome assembly (Gallus_gallus-5.0; GCA_000002315.3), built from combined long single molecule sequencing technology, finished BACs, and improved physical maps. In overall assembled bases, we see a gain of 183 Mb, including 16.4 Mb in placed chromosomes with a corresponding gain in the percentage of intact repeat elements characterized. Of the 1.21 Gb genome, we include three previously missing autosomes, GGA30, 31, and 33, and improve sequence contig length 10-fold over the previous Gallus_gallus-4.0. Despite the significant base representation improvements made, 138 Mb of sequence is not yet located to chromosomes. When annotated for gene content, Gallus_gallus-5.0 shows an increase of 4679 annotated genes (2768 noncoding and 1911 protein-coding) over those in Gallus_gallus-4.0. We also revisited the question of what genes are missing in the avian lineage, as assessed by the highest quality avian genome assembly to date, and found that a large fraction of the original set of missing genes are still absent in sequenced bird species. Finally, our new data support a detailed map of MHC-B, encompassing two segments: one with a highly stable gene copy number and another in which the gene copy number is highly variable. The chicken model has been a critical resource for many other fields of study, and this new reference assembly will substantially further these efforts